CN103655545B - The application of Jaceosidin in the medicine preparing treatment or preventing chronic injury of kidney - Google Patents
The application of Jaceosidin in the medicine preparing treatment or preventing chronic injury of kidney Download PDFInfo
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- GLAAQZFBFGEBPS-UHFFFAOYSA-N jaceosidin Chemical compound C1=C(O)C(OC)=CC(C=2OC3=CC(O)=C(OC)C(O)=C3C(=O)C=2)=C1 GLAAQZFBFGEBPS-UHFFFAOYSA-N 0.000 title claims abstract description 66
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to the application of Jaceosidin in the medicine preparing treatment or preventing chronic injury of kidney, be specifically related to Jaceosidin at preparation treatment or preventing chronic renal failure, the application in the medicine of renal fibrosis and diabetic nephropathy.In above-mentioned application, Jaceosidin using dosage scope is 10mg ~ 500mg; Preferably 10 ~ 250mg.Jaceosidin exists with forms such as tablet, pill, granule, capsule, syrup, is preferably tablet.
Description
Technical field
The present invention relates to the application of Jaceosidin in the medicine preparing treatment or preventing chronic injury of kidney, be specifically related to Jaceosidin at preparation treatment or preventing chronic renal failure, the application in the medicine of renal fibrosis and diabetic nephropathy.
Background technology
Folium Artemisiae Argyi (FoliumArtemisiaeArgyi) derives from the dried leaves of Compositae sagebruss Chinese mugwort (ArtemisiaargyiLevl.etVant.), is clinical conventional Chinese medicine.Jaceosidin is from Folium Artemisiae Argyi, extract the single compound [Tang Shengan obtained, Sun Liang, Zhai Huiyuan, Duan Hongquan, Zhang Yanwen. the research of Folium Artemisiae Argyi chemical composition. Medical University Of Tianjin's journal, 2011,17 (4): 461-463.], Jaceosidin has antiinflammatory action [ClavinM, GorzalczanyS, MachoA
e, FerraroG, AcevedoC, MartinoV.Anti-inflammatoryactivityofflavonoidsfromEupato riumamottianum.JEthnopharmaco1.2007; , but Jaceosidin has no report at preparation prevention or treatment Chronic Renal Impairment and the pharmacological action of renal fibrosis 112 (3): 585-589.].The present inventor, by a large amount of experimentatioies, has invented the application of Jaceosidin in the medicine preparing treatment or preventing chronic renal failure, renal fibrosis and diabetic nephropathy.
Summary of the invention:
The invention provides the application of Jaceosidin in the medicine preparing treatment or preventing chronic injury of kidney
The invention provides the application of Jaceosidin in the medicine preparing treatment or preventing chronic renal failure.
The invention provides the application of Jaceosidin in the medicine preparing treatment or preventing renal fibrosis.
The invention provides the application of Jaceosidin in the medicine preparing treatment or diabetes and nephropathy preventing.
Jaceosidin provided by the invention for chronic renal failure, renal fibrosis and diabetic nephropathy time, its using dosage scope is 10mg ~ 500mg; Preferably 10 ~ 250mg.
Jaceosidin provided by the invention according to preparation needs, can add corresponding adjuvant, exists, be preferably tablet with, the form such as tablet, pill, granule, capsule, syrup.Various dosage form provided by the invention all can adopt pharmacy conventional method to be prepared from.
Present inventor has performed following test to confirm the application in the medicine for the treatment of or preventing chronic renal failure, renal fibrosis and diabetic nephropathy, but pharmacological action is not limited thereto.
Concrete embodiment:
Preparation example 1: prepare Jaceosidin
The Folium Artemisiae Argyi of 1kg drying is pulverized, 3 times are extracted with the alcohol heating reflux of 6 times amount 95%, each 6h, filter, merging filtrate, be evaporated to extractum shape, obtain extract, after adding appropriate distilled water suspendible, with extraction into ethyl acetate in the separatory funnel of 10L, collect extract with silica gel column chromatography (silica gel 600g, 300-400 order) be separated, use CH2C12 → CH2C12:EtoAc (5:1 → 2:1) → EtoAc → MeOH gradient elution successively, merge similar components by TLC, cross silicagel column normal pressure post, obtain Jaceosidin 460mg.
Prepared by embodiment 2 Jaceosidin tablet
Cross 100 mesh sieves after taking 10.0g Jaceosidin, 55.0g Icing Sugar, 110.0g lactose and the abundant mix homogeneously of 23.0g carboxymethyl starch sodium, add appropriate 3%PVP
k30aqueous solution is soft material processed in right amount, and 20 mesh sieves are granulated, and 60 DEG C of dryings 3 hours, 18 mesh sieve granulate, add 2.0g magnesium stearate, and scrobicula punching press after mix homogeneously, adjustment sheet is 200mg heavily about, to obtain final product.
Specific embodiment
Test 1 Jaceosidin causes rat chronic renal failure impact on the nephrectomy
1.1 medicines and reagent
Jaceosidin is prepared by preparation example 1
Glutathion (Shandong Luye Pharmaceutical Co., Ltd., specification: 300mg/ props up, lot number: 20120706)
Creatinine and blood urea nitrogen test kit (Beijing Zhong Sheng scientific & technical corporation, lot number: 120606)
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, Shandong Luye Pharmaceutical Co., Ltd.'s animal experimental center provides.The quality certification number: No. 200906005, Shandong kinoplaszm word.
1.2 test methods and result
Rat 140, body weight 150-200g, animal feeding 1 week, animal is divided into 7 groups, often organize 20, i.e. normal group, model group, glutathion intravenous injection (150mg/kg) group, Jaceosidin 1mg/kg group, Jaceosidin 5mg/kg group, Jaceosidin 25mg/kg group, Jaceosidin 50mg/kg group, except normal group, rat 5/6 nephrectomy method makes chronic kidney hypofunction model, the left kidney 2/3 of first time excision, the right kidney of row second time excision after one week, second time Post operation starts administration in 5 weeks, Jaceosidin administering mode is gastric infusion, after administration 4 weeks, 8 weeks respectively large rathole frame get blood, measure serum creatinine and blood urea nitrogen, within after administration 4 weeks, put to death 10, off-test puts to death 10, make pathological section, observe the pathological change of renal function.
As can be seen from table 1, table 2 result, Jaceosidin 1mg/kg group reduces rat chronic renal failure serum creatinine and blood urea nitrogen (comparing with model group, p < 0.05); Glutathion intravenous injection (150mg/kg) group, Jaceosidin 5mg/kg group, Jaceosidin 25mg/kg group, Jaceosidin 50mg/kg group obviously reduces rat chronic renal failure serum creatinine and blood urea nitrogen (comparing with model group, p < 0.01); Jaceosidin 25mg/kg group reduces rat chronic renal failure serum creatinine and blood urea nitrogen compares with Jaceosidin 50mg/kg group, there was no significant difference.
Pathological change: administration is shown in that glomerule has compensatory hypertrophy in various degree, proliferation of mesangial cells under model group light microscopic on the 4th week, and extracellular matrix increases, glomerular capillary button loop is in lobulated, and part glomerule blister cavities disappears, blood capillary tube wall thickening, renal tubules swelling, expansion, have proteinosis in tube chamber, part tubular atrophy, interstitial has inflammatory cell infiltration, each administration group is also shown in above-mentioned change, but lesion degree is comparatively light, increase with dosage, lesion degree alleviates; Administration is shown in proliferation of mesangial cells under model group light microscopic on the 8th week, substrate showed increased, blood capillary tube wall subsides, blood capillary segmented sclerosis, in the many glomerule hardened near blood vessel wall in harden zone, the circular PAS of visible homogenizing dyes wine-colored deposit, indivedual glomerule has focal adhosion, focal diffuse crescent formation, and interstitial visible inflammatory cell infiltrates, proliferation of fibrous tissue, each group of glomerular sclerosis varying degree, increase with dosage, lesion degree alleviates.
Table 1 Jaceosidin is on the impact of nephrectomy CRF rats administration 4 weeks serum creatinines and blood urea nitrogen
*, p < 0.05,
*, p < 0.01, compares with model group
Table 2 Jaceosidin is on the impact of nephrectomy CRF rats administration 8 weeks serum creatinines and blood urea nitrogen
*, p < 0.05,
*, p < 0.01, compares with model group
Test the impact of 2 Jaceosidins on Rats Undergoing Unilateral Urethral Ligation kidney region fibrosis
2.1 material
Jaceosidin is prepared by preparation example 1
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, Shandong Luye Pharmaceutical Co., Ltd.'s animal experimental center provides.The quality certification number: No. 200906005, Shandong kinoplaszm word.
Enalapril, Novartis Pharma AG produces, lot number: 040306; Hydroxyproline test kit, biotech firm is built up in Nanjing, lot number: 050906.
2.2 test methods and result
Rat 70, body weight 200-230g, animal feeding 1 week, each rat is with after 10% chloral hydrate 3.0mL/kg intraperitoneal injection of anesthesia, Rat Right lateral position is fixed on operating-table, with iodine tincture after cropping, 75% alcohol disinfecting field of operation, row left side abdomen otch, successively cut skin, muscle and each layer of stomach wall, expose and be separated left side ureter, wherein 10 rats only cut abdominal cavity and free left side ureter, but not ligation and cutting off, as sham operated rats, all the other 60 rats 4-0 silk thread ligation twice, upper one ligation point is positioned at left inferior pole of kidney level, then between twice ligation point, ureter is cut off, layer-by-layer suture, 60 modeling rats are divided into 6 groups at random, i.e. model group, enalapril (4mg/kg) group, Jaceosidin 1mg/kg group, Jaceosidin 5mg/kg group, Jaceosidin 25mg/kg group, Jaceosidin 50mg/kg group, each group of administration is after 21 days, each treated animal is put to death after 10% chloral hydrate anesthesia, normal saline leaves and takes left kidney after lavation repeatedly, nephridial tissue is fixed through the paraformaldehyde buffer of 4%.Cut appropriate nephridial tissue, illustrate by hydroxyproline kit measurement and measure hydroxyproline.
As can be seen from Table 3, Jaceosidin 1mg/kg group, enalapril (4mg/kg) group, Jaceosidin 5mg/kg group, Jaceosidin 25mg/kg group, Jaceosidin 50mg/kg group obviously reduces rat hydroxyprolin levels (comparing with model group, p < 0.05 or 0.01), Jaceosidin 25mg/kg group reduces hydroxyprolin levels and compares with Jaceosidin 50mg/kg group, there was no significant difference.Routine pathology checks 1. macroscopy: sham operated rats kidney color is scarlet, smooth surface, and peplos gloss, without adhesion.Other are the increase of group Kidney Volume respectively, and color is pale, and surface is graininess, similar human body branny kidney, the adhesion of a few regions kidney peplos.2. light microscopy checking: sham operated rats nephron clear in structure, glomerular capsule is without expansion or reduce, and renal cells is without obvious degeneration and necrosis, and tube chamber is interior without Exfoliative cells or cast, without vasodilation or cell infiltration in interstitial.The large stretch of renal tubular necrosis of model control group, renal interstitial fibroblast proliferation, tubular ectasia, inside has the epithelial cell that a large amount of brown color refractive power material or necrosis come off, glomerule decreased number, part glomerule fibrosis and with the adhesion of bowman's capsule wall, blister cavities disappears.Administration respectively organizes pathological changes and model control group is similar, but all has morphology in various degree to improve, and especially with the heavy dose of each group of Jaceosidin significantly, compares, obvious difference with model control group.
Table 3 Jaceosidin is on the impact of Rats Undergoing Unilateral Urethral Ligation nephridial tissue hydroxyproline content
P < 0.05,
*, p < 0.01, compares with model group
Test the impact of 3 Jaceosidins on diabetic nephropathy rats
3.1 material
Jaceosidin is prepared by preparation example 1
Enalapril, Novartis Pharma AG produces, lot number: 110306; Streptozotocin (Sigma company), blood sugar detection test kit (Beijing Zhong Sheng reagent company limited lot number: 120503); Creatinine and blood urea nitrogen test kit (Beijing Zhong Sheng scientific & technical corporation, lot number: 120606).
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, Shandong Luye Pharmaceutical Co., Ltd.'s animal experimental center provides.The quality certification number: No. 200906005, Shandong kinoplaszm word.
3.2 test methods and result
Male SD rat 100, after adaptability feeds 1 week, all rats are at 10% chloral hydrate (0.35mL/100g, ip) anaesthetize, the left kidney enucleation of row, the streptozotocin solution 60mg/kg of single intravenous injection 1% after one week, streptozotocin is with 0.1mol/L, pH is that 4.5 citric acid buffer solution dissolve, 72h posterior orbit is taken a blood sample, blood sugar detection kit measurement, blood glucose >=16.7mmol/L is defined as modeling success, 6 groups are divided at random after 4 weeks, i.e. model group, enalapril (2mg/kg) group, Jaceosidin 1mg/kg group, Jaceosidin 5mg/kg group, Jaceosidin 25mg/kg group, Jaceosidin 50mg/kg group, get 10 in addition as rats in normal control group.Each group of successive administration 4 weeks, eye socket blood sampling measures serum creatinine and blood urea nitrogen and each group rat 24h excretion quantity of urinary protein.Successive administration got blood after 4 weeks again, measured serum creatinine and blood urea nitrogen and respectively organized rat 24h excretion quantity of urinary protein, carrying out micrography simultaneously to kidney as pathological section.
Blood parameters measures: table 4, table 5 result shows Jaceosidin 1mg/kg group, enalapril (2mg/kg) group, Jaceosidin 5mg/kg group, Jaceosidin 25mg/kg group, Jaceosidin 50mg/kg group administration 4 weeks and obviously reduce serum creatinines and blood urea nitrogen and 24h excretion quantity of urinary protein (comparing with model control group, p < 0.05 or 0.01) for 8 weeks; Jaceosidin 25mg/kg group reduces serum creatinine and blood urea nitrogen and 24h excretion quantity of urinary protein and compares with Jaceosidin 50mg/kg group, there was no significant difference.
Pathologic finding: rats in normal control group glomerular basement membrane is normal, has no broadening, podocytic process marshalling.Model control group Renal Glomeruli In Rats basement membrane is significantly broadening, podocytic process arrangement disorder, fusion, mesangial cell and the slight segmental hypertrophy of substrate.The each administration group of Jaceosidin comparatively model group pathological changes is light, and progressively alleviates with the increase pathology of dosage.
The table 4 Jaceosidin administration impact on diabetic nephropathy rats in 4 weeks (n=10)
*, p < 0.05,
*, p < 0.01, compares with model group
The table 5 Jaceosidin administration impact on diabetic nephropathy rats in 8 weeks (n=10)
*, p < 0.05,
*, p < 0.01, compares with model group.
Claims (1)
1. the application of Jaceosidin in the medicine of preparation treatment renal fibrosis, wherein when Jaceosidin treatment or preventing renal fibrosis, oral medication is 250mg.
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